Re-considering how particle size and other properties of antigen-adjuvant complexes impact on the immune responses

Understanding the influences of particle properties of antigen-adjuvant complexes on immunity is crucial in designing highly active adjuvants for new-generation of vaccines. This paper briefly revisits the current opinions on the size-dependent immunity of various adjuvant particles and then comprehensively discusses a few immunity-determining processes that are affected by the antigen-adjuvant particle properties. These include particle size, surface charge, surface hydrophilicity/lipophilicity, and antigen-adjuvant binding strength. Based on current understandings, we hypothesize that a maximum immune response occurs at a certain antigen-adjuvant particle size. This hypothesis clearly explains the paradoxical opinions on the size-dependent immunity and has also been supported by the data reported by several research groups. Finally, we further hypothesize that there is a similar relationship between any immune response and any measureable antigen-adjuvant particle property, and that there is a maximum immune response when all measureable antigen-adjuvant particle properties are optimized. We believe more attention should be paid to this issue when designing and developing effective adjuvants in future research.